Department of Biochemistry and Molecular Biology, Kyoto Pharmaceutical University, Kyoto, Japan.
FASEB J. 2019 Mar;33(3):3936-3953. doi: 10.1096/fj.201801369R. Epub 2018 Nov 29.
Heat shock causes proteotoxic stress that induces various cellular responses, including delayed mitotic progression and the generation of an aberrant number of chromosomes. In this study, heat shock delayed the onset of anaphase by increasing the number of misoriented cells, accompanied by the kinetochore localization of budding uninhibited by benzimidazole-related (BubR)1 in a monopolar spindle (Mps)1-dependent manner. The mitotic delay was canceled by knockdown of mitotic arrest defect (Mad)2. Knockdown of heat shock protein (Hsp)105 partially abrogated the mitotic delay with the loss of the kinetochore localization of BubR1 under heat shock conditions and accelerated mitotic progression under nonstressed conditions. Consistent with this result, Hsp105 knockdown increased the number of anaphase cells with lagging chromosomes, through mitotic slippage, and decreased taxol sensitivity more than Mad2 knockdown. Hsp105 was coprecipitated with cell division cycle (Cdc)20 in an Mps1-dependent manner; however, its knockdown did not affect coprecipitation of Mad2 and BubR1 with Cdc20. We propose that heat shock delays the onset of anaphase via the activation of the spindle assembly checkpoint (SAC). Hsp105 prevents abnormal cell division by contributing to SAC activation under heat shock and nonstressed conditions by interacting with Cdc20 but not affecting formation of the mitotic checkpoint complex.-Kakihana, A., Oto, Y., Saito, Y., Nakayama, Y. Heat shock-induced mitotic arrest requires heat shock protein 105 for the activation of spindle assembly checkpoint.
热休克导致蛋白毒性应激，诱导各种细胞反应，包括延迟有丝分裂进程和产生异常数量的染色体。在这项研究中，热休克通过增加错位细胞的数量来延迟后期的开始，伴随着在单极纺锤体（Mps）1 依赖性方式下，着丝粒定位的芽殖不受苯并咪唑相关（BubR）1 的抑制。有丝分裂阻滞缺陷（Mad）2 的敲低消除了有丝分裂延迟。热休克蛋白（Hsp）105 的敲低部分消除了热休克条件下 BubR1 的着丝粒定位的有丝分裂延迟，并在非应激条件下加速有丝分裂进程。与这一结果一致，Hsp105 的敲低通过有丝分裂滑动增加了滞后染色体的后期细胞数量，并增加了紫杉醇敏感性，比 Mad2 敲低更明显。Hsp105 以 Mps1 依赖性方式与细胞分裂周期（Cdc）20 共沉淀；然而，其敲低并不影响 Mad2 和 BubR1 与 Cdc20 的共沉淀。我们提出，热休克通过激活纺锤体组装检查点（SAC）来延迟后期的开始。Hsp105 通过与 Cdc20 相互作用，在热休克和非应激条件下有助于 SAC 的激活，从而防止异常细胞分裂，但不影响有丝分裂检查点复合物的形成。
